Assisted hydrolysis of cis-2-(3-phenylthioureido)cyclo pentane-carbonitrile in alkaline solution. Solvent dependent switch from hydrolysis to rearrangement of the iminothiooxopyrimidine intermediate
The cis and trans isomers of 2-(3-phenylthioureido)cyclopentanecarbonitrile, 1 , and the respective carboxamides, 3 , and acids, 4 , have been prepared. Acid cyclization of both nitriles, faster with the cis isomer, gave the more stable cis-2-thiooxo-cyclopenta[d]pyrimidin-4-one, 7 . In base cis- 1...
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Veröffentlicht in: | Canadian journal of chemistry 2000-01, Vol.78 (1), p.84-94 |
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Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | The cis and trans isomers of 2-(3-phenylthioureido)cyclopentanecarbonitrile,
1
, and the respective carboxamides,
3
, and acids,
4
, have been prepared. Acid cyclization of both nitriles, faster with the cis isomer, gave the more stable cis-2-thiooxo-cyclopenta[d]pyrimidin-4-one,
7
. In base cis-
1
formed the cis 4-imino-2-thiooxopyrimidine
2
which in aqueous alkali broke down via
3
to the acid
4
; while in the presence of 66% acetonitrile
2
rearranged to the 4-phenyliminopyrimidine
5
to give as final product the thioureido acid
6
carrying no phenyl group. The
1
H NMR data for imino and phenylimino derivatives
2
and
5
showed strong bias for conformation
A
with 1-N pseudoaxial in the cyclopentane ring. Spectra of the E andZ isomers of the iminopyrimidine
2
under slow exchange could be recorded in DMSO-d
6
. The phenylimino tautomer of
5
is observed in CD
3
OD and in CDCl
3
with the E and Z isomers in a 1:1 ratio. In DMSO-d
6
the phenylamino tautomer
5a
is also detected. The first process in aqueous KOH, the conversion of nitrile cis-
1
into the imino intermediate
2
, reaches an equilibrium which shifts towards the nitrile at higher alkalinities because of ionization of the phenylthioureido group (K
e
= [
2
]/[
1
] = 2.43 and pK
AH
= 12.74). The cyclization of
1
to
2
is first order in [OH
-
] while the slower breakdown of
2
is pH independent. The latter is 10
4
times faster than the hydrolysis of acetonitrile evidencing substantial anchimeric assistance. The change in the reaction route towards the rearranged phenyliminopyrimidine
5
upon addition of acetonitrile can be caused by the lower dielectric constant favouring the elimination step leading to the intermediate isothiocyanate, and by increased activity of OH
-
accelerating the (presumably) second order elimination step as opposed to the pH-independent hydrolysis of the imino derivative
2
. Key words: anchimeric assistance, phenylthioureido nitriles, iminothiooxopyrimidine tautomers, alkaline hydrolysis, solvent effects. |
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ISSN: | 0008-4042 1480-3291 |
DOI: | 10.1139/v99-216 |